Different electric and magnetic field (E/MF) configurations have been applied for non-invasive imaging therapies and surgery (laser) for many years. Unlike their higher energy counterparts, the biological mechanisms underlying the effects of exposure to low-power E/MF remain largely uncharacterized while therapeutic applications are beginning to emerge. Some cellular research themes have emerged in the last decade to help bridge the understanding of fundamental cellular responses to weak E/MFs, into therapeutic pathways. In this context, the salient theme driving this proposal parse into two main themes with respect to weak E/MF exposure: (i) inactivation of cells, and (ii) sub-lethal doses that activate or otherwise affect different cellular functions. Our objective is to establish dose-response thresholds for bacterial and eukaryotic cells on a on a fundamental biophysical level, which maps into understanding (and controlling) organized cellular-system response in weak E/MF fields. The central hypothesis driving these investigations is: that the effects of E/MF on bacterial and eukaryotic cells have common mechanistic bases. We believe we can elucidate fundamental biological responses to E/MF exposures by leveraging the respective strengths of widely-accepted cell culture practices with modern biochemical and transcriptome analyses. We have engineered bench-scale experimental apparati to isolate and combine electric and magnetic fields of various strengths;these systems permit real-time, direct microscopic access to cells as they are suspended in electromagnetic fields. We can thus observe intra- and intercellular E/MF responses (both physical and chemical) in real time, and establish threshold values for lethal and sub-lethal EM doses. We will investigate the effect of AC, DC and (isolated) magnetic field exposure utilizing the strengths of these experimental systems. We will juxtapose our cellular-level findings to leukocyte motility models, and investigate how mechanistic observations can be applied to systems with therapeutic benefits. Relevance: A mechanistic understanding of the effects weak E/MF have on biological systems will aid in the design, engineering and operations of therapeutic devices that currently utilize E/MF, or may do so in the near future.